Since enzymes and other biological receptors possess chiral centers, enantiomers of a racemic compound may be absorbed, activated, and degraded by them in different manners. Due to this phenomenon, in many instances, two enantiomers of a racemic drug may have very different pharmacological activities. Recognizing the importance of chirality in drug development, the US Food and Drug Administration (FDA) issued guidelines in 1992 regarding the stereoisomers of drugs with chiral centers. Since then, drugs are increasingly marketed as pure enantiomers. To develop such enantiomerically pure drugs, techniques for chiral separations are in high demand. They are needed for analytic separations to determine the enantiomerical purity of analytes. They are also widely used as efficient methods to provide quick access to reasonable amounts of enantiomerically pure materials in order to assess their pharmaceutical activity in drug development. Among the asymmetric technologies developed to analyze and separate optically active compounds, the direct separation of enantiomers by HPLC on chiral stationary phases has been a subject of intense investigation. As a result, a wide variety of chiral stationary phases have been developed. Although a thorough evaluation of all the current chiral columns is impossible, the commonly used chiral columns do seem to have some limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This AREA proposal is intended to continue the PI's efforts to develop efficient stationary phases for chiral chromatography. Specific aims include further improvement of the oligoproline chiral selectors, newer types of oligoproline chiral stationary phases, and the application of proline chiral selectors to other separation methods. If the aims of the proposal are successfully achieved, enantiomerically pure compounds could be made readily available. These compounds are very important in drug development, as many drugs are either commercialized in enantiomerically pure form or developed from enantiomerically pure compounds.